The amyloid plaques in the brains of AD patients consist of fibrils formed by Aβ. Aβ is produced from amyloid precursor protein (APP) by sequential proteolytic cleavages of β-secretase (β-site APP-cleaving enzyme, BACE) and γ-secretase (Fig. 1)9. In the amyloidogenic pathway of APP processing, APP is initially cleaved by BACE, resulting in soluble APPβ (sAPPβ) and membrane-bound APP-CTF (C99)9. C99 is further cleaved by γ-secretase to release Aβ extracellularly and the APP intracellular domain (AICD) for nuclear translocation9. Alternatively, APP is cleaved by α-secretase to produce sAPPα and APP-CTF (C83) (Fig. 1)9. C83 is further cleaved by γ-secretase to produce p3 and AICD9.
In the amyloidogenic pathway, β-secretase cleaves APP extracellularly to release sAPPβ and a membrane-bound APP-CTF (C99). C99 is subsequently cleaved by γ-secretase to…
